Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion

2004 ◽  
Vol 287 (4) ◽  
pp. H1522-H1529 ◽  
Author(s):  
Chris J. Pemberton ◽  
Heikki Tokola ◽  
Zsolt Bagi ◽  
Akos Koller ◽  
Juhani Pöntinen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natriuretic Peptide ◽  
Cardiac Tissue ◽  
Contractile Function ◽  
Isolated Heart ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Neonatal Cardiomyocytes ◽  
Peptide Secretion ◽  
Coronary Arterioles

We administered ghrelin, a novel growth hormone-releasing hormone, to isolated perfused rat hearts, coronary arterioles, and cultured neonatal cardiomyocytes to determine its effects on coronary vascular tone, contractility, and natriuretic peptide secretion and gene expression. We also determined cardiac levels of ghrelin and whether the heart is a source of the circulating peptide. Ghrelin dose dependently increased coronary perfusion pressure (44 ± 9%, P < 0.01), constricted isolated coronary arterioles (12 ± 2%, P < 0.05), and significantly enhanced the pressure-induced myogenic tone of arterioles. These effects were blocked by diltiazem, an L-type Ca2+ channel blocker, and bisindolylmaleimide (Bis), a protein kinase C (PKC) inhibitor. Interestingly, coinfusion of ghrelin with diltiazem completely restored myocardial contractile function that was decreased 30 ± 3% ( P < 0.01) by diltiazem alone. In contrast, combination of ghrelin with diltiazem or Bis did not significantly alter atrial natriuretic peptide (ANP) secretion, which was decreased 40% ( P < 0.01) and 50% ( P < 0.05) by these agents alone, respectively. Administration of ghrelin to cultured cardiomyocytes had no effect on ANP or B-type natriuretic peptide secretion or gene expression. Detectable amounts of low-molecular-weight ghrelin were present in cardiac tissue extracts but not in isolated heart perfusate. Thus we provide the first evidence that ghrelin has a coronary vasoconstrictor action that is dependent on Ca2+ and PKC. Furthermore, the data obtained from diltiazem infusion suggest that ghrelin has a role in regulation of contractility when L-type Ca2+ channels are blocked. Finally, the observation that immunoreactive ghrelin is found in cardiac tissue suggests the presence of a local cardiac ghrelin system.

Downregulation of ventricular contractile function during early ischemia is flow but not pressure dependent

1998 ◽  
Vol 275 (5) ◽  
pp. H1520-H1523 ◽  
Author(s):  
Miao-Xiang He ◽  
H. Fred Downey
Keyword(s):  
Coronary Artery ◽  
Perfusion Pressure ◽  
Contractile Function ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Rat Hearts ◽  
Myocardial Contractile Force ◽  
Myocardial Contractile ◽  
Artery Obstruction

The mechanism responsible for the abrupt fall in myocardial contractile function following coronary artery obstruction is unknown. The “vascular collapse theory” hypothesizes that the fall in coronary perfusion pressure after coronary artery obstruction is responsible for contractile failure during early ischemia. To test the role of vascular collapse in downregulating myocardial contractile force at the onset of ischemia, coronary flow of isolated rat hearts was abruptly decreased by 50, 70, 85, and 100% of baseline, and subsequent changes in coronary perfusion pressure and ventricular function were recorded at 0.5-s intervals. At 1.5 s after flow reductions ranging from 50 to 100%, decreases in contractile function did not differ, although perfusion pressure varied significantly from 45 ± 1 to 20 ± 2 mmHg. When function fell to 50% of baseline, perfusion pressures ranged from 35 ± 0.5 to 2.5 ± 1 mmHg for flow reductions ranging from 50 to 100%. Identical contractile function at widely differing coronary perfusion pressures is incompatible with the vascular collapse theory.

scholarly journals Gene expression changes controlling distinct adaptations in the heart and skeletal muscle of a hibernating mammal

2015 ◽  
Vol 47 (3) ◽  
pp. 58-74 ◽  
Author(s):  
Katie L. Vermillion ◽  
Kyle J. Anderson ◽  
Marshall Hampton ◽  
Matthew T. Andrews
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cardiac Tissue ◽  
Contractile Function ◽  
Oxygen Demand ◽  
Oxidative Capacity ◽  
Disuse Atrophy ◽  
Functional Requirements ◽  
Skeletal Muscle Function ◽  
Illumina Hiseq

Throughout the hibernation season, the thirteen-lined ground squirrel ( Ictidomys tridecemlineatus) experiences extreme fluctuations in heart rate, metabolism, oxygen consumption, and body temperature, along with prolonged fasting and immobility. These conditions necessitate different functional requirements for the heart, which maintains contractile function throughout hibernation, and the skeletal muscle, which remains largely inactive. The adaptations used to maintain these contractile organs under such variable conditions serves as a natural model to study a variety of medically relevant conditions including heart failure and disuse atrophy. To better understand how two different muscle tissues maintain function throughout the extreme fluctuations of hibernation we performed Illumina HiSeq 2000 sequencing of cDNAs to compare the transcriptome of heart and skeletal muscle across the circannual cycle. This analysis resulted in the identification of 1,076 and 1,466 differentially expressed genes in heart and skeletal muscle, respectively. In both heart and skeletal muscle we identified a distinct cold-tolerant mechanism utilizing peroxisomal metabolism to make use of elevated levels of unsaturated depot fats. The skeletal muscle transcriptome also shows an early increase in oxidative capacity necessary for the altered fuel utilization and increased oxygen demand of shivering. Expression of the fetal gene expression profile is used to maintain cardiac tissue, either through increasing myocyte size or proliferation of resident cardiomyocytes, while skeletal muscle function and mass are protected through transcriptional regulation of pathways involved in protein turnover. This study provides insight into how two functionally distinct muscles maintain function under the extreme conditions of mammalian hibernation.

Cytosolic Ca2+ during atrial natriuretic peptide secretion from cultured neonatal cardiomyocytes

1990 ◽  
Vol 73 (2-3) ◽  
pp. 153-163 ◽  
Author(s):  
Paavo A. Uusimaa ◽  
Heikki Ruskoaho ◽  
Juhani Leppäluoto ◽  
Ilmo E. Hassinen
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Neonatal Cardiomyocytes ◽  
Peptide Secretion ◽  
Atrial Natriuretic

scholarly journals Effect of valsartan on cardiac senescence and apoptosis in a rat model of cardiotoxicity

2016 ◽  
Vol 94 (6) ◽  
pp. 588-598 ◽  
Author(s):  
Hussein F. Sakr ◽  
Amr M. Abbas ◽  
Ayman Z. Elsamanoudy
Keyword(s):  
Gene Expression ◽  
Cardiac Tissue ◽  
Isolated Heart ◽  
Left Ventricular ◽  
Creatine Kinase Mb ◽  
Heart Lipid ◽  
Total Antioxidant ◽  
Pre Treatment ◽  
Developed Pressure ◽  
Bax Gene

The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and −dP/dtmax and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dtmax. Also, doxorubicin lengthened ST, QT, and QTc intervals. Concurrent or post- but not pre-treatment of doxorubicin-treated rats with valsartan reduced LDH, CK-MB, TBARS, HR, Bax gene expression, −dP/dtmax, and ST, QT, and QTc intervals and increased TAC, Bcl-2 and SMP30 gene expression, LVDP, and +dP/dtmax. Therefore, we conclude that concurrent or post- but not pre-treatment of doxorubicin-induced rats with valsartan attenuated doxorubicin-induced cardiotoxicity through inhibiting oxidative stress, apoptosis, and senescence.

Free radicals upregulate complement expression in rabbit isolated heart

2000 ◽  
Vol 279 (1) ◽  
pp. H195-H201 ◽  
Author(s):  
Elaine J. Tanhehco ◽  
Koji Yasojima ◽  
Patrick L. McGeer ◽  
Ruth A. Washington ◽  
Benedict R. Lucchesi
Keyword(s):  
Free Radicals ◽  
Complement Activation ◽  
Diastolic Pressure ◽  
Tissue Injury ◽  
Isolated Heart ◽  
Membrane Attack Complex ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Isolated Hearts

Both free radicals and complement activation can injure tissue. Our study determined whether free radicals alter complement production by the myocardium. Isolated hearts from New Zealand White rabbits were perfused on a Langendorff apparatus and exposed to xanthine (X; 100 μM) plus xanthine oxidase (XO; 8 mU/ml) (X/XO). The free radical-generating system significantly ( P < 0.05) increased C1q and also increased C1r, C3, C8, and C9 transcription compared with controls. Immunohistological examination revealed augmented membrane attack complex deposition on X/XO-treated tissue. X/XO-treated hearts also exhibited significant ( P < 0.05) increases in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in left-ventricular developed pressure. N-(2-mercaptopropionyl)-glycine (3 mM), in conjunction with the superoxide dismutase mimetic SC-52608 (100 μM), significantly ( P < 0.05) reduced the upregulation of C1q, C1r, C3, C8, and C9 mRNA expression elicited by X/XO. The antioxidants also ameliorated the deterioration in function caused by X/XO. Local complement activation may represent a mechanism by which free radicals mediate tissue injury.

scholarly journals Morphological and functional changes of coronary vasculature caused by transcellular biosynthesis of sulfidopeptide leukotrienes in isolated heart of rabbit

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1824-1832 ◽  
Author(s):  
A Sala ◽  
GM Aliev ◽  
G Rossoni ◽  
F Berti ◽  
C Buccellati ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Isolated Heart ◽  
Rabbit Heart ◽  
Coronary Perfusion Pressure ◽  
Coronary Vasospasm ◽  
Coronary Perfusion ◽  
Lipoxygenase Inhibitor ◽  
Morphological Alterations ◽  
Functional Changes ◽  
Macrophage Colony

Morphological and functional modifications occurring in Langendorff rabbit heart preparations perfused with purified human leukocytes (PMNL), as an organ model of sulfidopeptide-leukotrienes (sLT) transcellular biosynthesis, were studied. Coronary perfusion pressure (CPP), monitored as an index of coronary vasospasm, increased by 295% after challenge with the Ca(2+)-ionophore A-23187 (0.5 micromol/L) for 30′, accompanied by a significant formation of sLT. Increase in CPP was prevented by PMNL pretreatment with the 5-lipoxygenase inhibitor MK-886 (1 micromol/L) or by heart pretreatment with LTD4-receptor antagonist SKF 104353, indicating a pivotal role of PMNL-derived 5-lipoxygenase (5- LO) products in the observed functional modifications. Similar effects were obtained using granulocyte macrophage-colony stimulating factor- primed PMNL challenged with the tripeptide n-formyl-methionyl-leucyl- phenylalanine. Scanning electron microscopy (SEM) of coronary arteries showed craters on the vessel luminal surface, PMNL adhering to endothelial cells (EC), increased number of microvilli on EC, presence of nonviable, desquamating, fusiform EC. SEM and transmission electron microscopy of myocardial microvessels, showed presence of perivascular and intermuscle edema, presence of activated PMNL and decreased number of patent microvessels. These morphological alterations were significantly blunted by MK-886 or SKF 104353. These data provide evidence of close interaction between PMNL and myocardial EC, resulting in enhanced sLT formation via transcellular biosynthesis, originating from transfer of PMNL-derived LTA4 to EC. These potent proinflammatory autacoids are responsible for coronary vasospasm and the morphological alternations observed.

Left ventricular performance and blood catecholamine levels in the isolated heart

1966 ◽  
Vol 211 (5) ◽  
pp. 1248-1254 ◽  
Author(s):  
R. Grier Monroe ◽  
C. G. La Farge ◽  
W. J. Gamble ◽  
R. P. Hammond ◽  
R. Gamboa
Keyword(s):  
Diastolic Pressure ◽  
Isolated Heart ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Left Ventricular Performance ◽  
Ventricular Performance ◽  
Isolated Lungs ◽  
Catecholamine Levels ◽  
Catecholamine Concentration

Left ventricular performance in the isolated heart of the dog as expressed by the peak systolic intraventricular pressure was observed during control periods when the heart was perfused with blood from a healthy anesthetized donor and after the donor was removed and the heart perfused with blood oxygenated by isolated lungs. Heart rate, coronary perfusion pressure, ventricular end-diastolic pressure, and stroke volume were maintained constant throughout. While the heart was perfused with blood from a donor, ventricular performance showed no tendency to decline, although coronary flow invariably increased. On removing the donor and perfusing the heart with blood oxygenated by isolated lungs, myocardial performance declined in proportion to the decline in the total catecholamine concentration of the perfusing blood. Restoration of catecholamine levels by infusing epinephrine and norepinephrine also restored left ventricular performance.

Sign in / Sign up

Export Citation Format

Share Document